Ferret Neoplasia By Dr. Teresa Lightfoot, DVM, DABVP Insulinomas (Beta cell carcinomas of the pancreas)

Ferret Neoplasia

By Dr. Teresa Lightfoot, DVM, DABVP

Insulinomas (Beta cell carcinomas of the pancreas)

Insulinomas of ferrets are a common clinical finding after a ferret reaches three to four years
of age. Hypoglycemia is the result of an active and advanced insulinoma, and may present
as weakness, lethargy, anorexia (due most likely to nausea), or stupor.1,2,10,16,18,19 A blood
glucose is often diagnostic, even without fasting. Generally, clinically affected ferrets will
display blood glucose levels between 20 - 60 g/dl, and at these levels this is diagnostic.
Ferrets brought in earlier in the course of the disease may have blood glucose levels in the
high 70’s and require a four-hour fast to confirm the diagnosis. Interestingly, several young
ferrets (less than three years of age) have had insulinomas discovered during exploratory
surgery for gastrointestinal foreign bodies. The blood glucose levels of these ferrets were
still within the normal range. The actual age of onset of the formation of these tumors is not
known, but it is likely that they exist asymptomatically in many ferrets for prolonged periods.
Insulin/glucose ratios are available and useful diagnostically when performed by a laboratory
that has verified their accuracy in ferrets. Initial treatment of the acute, laterally recumbent,
hypoglycemic, hypothermic ferret is I.V. dextrose, and the results are usually dramatic.
Concurrent therapy with a rapid acting glucocorticoid and the subsequent oral intake of
calories, especially fat and protein, is necessary to prevent reactive hypoglycemia that can
occur if I.V. dextrose therapy is used alone.

Ferrets with insulinomas may also present with a hypoglycemia-induced weakness, reported
as rear end paresis or ataxia, and this has historically been confused with spinal or disc
trauma. The positive clinical response to a glucocorticoid injection (which raises the blood
glucose) perpetuates the belief that the problem was musculoskeletal.

Treatment of insulinoma consists of surgical resection of visibly affected portions of the
pancreas. These may be discrete, visible or only palpable, pancreatic nodules, or
generalized areas of abnormal tissue. Although a positive clinical response to surgery is
usually noted, the neoplasia has generally micro-metastasized to other parts of the
pancreas prior to the onset of clinical signs. The use of prednisone (at 0.5 – 4.0 mg/kg
divided BID) as either the initial treatment, or as the treatment subsequent to surgical
resection if and when hypoglycemia recurs, will often increase the quality and length of
life.2,10,16,18 Diazoxide (Proglycem - @ 5-25 mg/kg B-TID) can be added to aid in
maintaining blood glucose, but it is expensive and in some practitioners’ experience,
minimally effective. It may allow the reduction of the prednisone dose, but it will not
substitute for prednisone therapy.

Ferret Insulinoma

Insulinomas are pancreatic islet cell tumors of the insulin-secreting beta cells. Insulinomas
are one of the most common tumors found in middle-aged to older ferrets in the United
States. Clinical signs may include intermittent lethargy, mental dullness, irritability,
hypersalivation, pawing at the mouth, weight loss, weakness in the hind limbs, and in severe
cases, seizures, coma or death. These signs may occur acutely or have a gradual onset
with increasing severity over several weeks to months. Blood glucose measurements of
less than 70 mg/dL suggest insulinoma. Normal blood glucose values for ferrets are
reported to range from 90 to 120 mg/dL. In this author’s experience, young, healthy ferrets
will exhibit blood glucose levels (when venipuncture is accomplished without anesthesia), of
over 110 mg/dL.

Ferrets with insulinoma often have blood glucose levels that fluctuate. Drawing blood after a
four to six hour fast or using serial blood glucose measurements will be more accurate
diagnostically. Fasting is contraindicated if clinical signs of hypoglycemia are apparent.
Blood insulin levels may also help in making a presumptive diagnosis. Ferrets with
insulinomas are reported to have insulin values from 107.7 to 1738 µU/mL. Normal values

are reported to be 15 to 35 µU/mL. Abnormally high insulin concentrations in association
with low blood glucose levels are indicative of insulinoma. A normal insulin concentration
with an abnormally low blood glucose does not rule out insulinoma. Exploratory laparotomy
is the definitive diagnostic approach. Micro-metastasis throughout the pancreas has usually
occurred by the time a diagnosis is made. The incidental finding of insulinomas during
gastric foreign body removal in ferrets less than two years of age indicates that these
neoplasias may be present for prolonged periods prior to the onset of clinical disease.
Surgery is rarely curative but functions to debulk the visible tumor tissue in an attempt to
slow the progression of the disease. Medical treatment will be required at some future point
as the disease progresses. The owner should be forewarned that management of this
disease will be required for the rest of the patient’s life. Medical treatment is aimed at
maintaining a blood sugar level that provides for the ferret’s comfortable existence.
Prednisone at 0.10 to 0.50 mg/kg orally every 12 hours will serve to increase the blood
sugar via several physiologic mechanisms. Ferrets on prednisone therapy often do better
clinically than their blood glucose levels would suggest, probably also due to the multiple
effects of glucocorticoid administration. As the disease progresses, the dose is increased
as needed, often to levels as high as 2.0 mg/kg to approximate euglycemia. When
prednisone alone fails to control the hypoglycemia, diazoxide at 5 to 30 mg/kg orally twice a
day can be added to the treatment protocol. The recommended diet is a high quality ferret
food ad lib. Sugary snacks should be avoided, as they tend to cause a rebound increase in
insulin. Eventually, the hypoglycemia will no longer be controllable medically or surgically.

Concurrent problems are extremely common in ferrets 3 years of age and older.
Cardiomyopathy, lymphoma, adrenal gland disease and skin tumors are present in many
ferrets with insulinoma. A thorough physical exam is important. A complete blood count
and serum chemistry panel should be performed to ensure general health and to rule out
concurrent illness. Insulinomas are often presumptively diagnosed during the presurgical
workup for another disease when the blood glucose is revealed to be less than 70 mg/dL.

Ultrasonography, when available, may be used to screen for concurrent diseases and will
detect large insulinomas although most are too small to be detected via ultrasound.
Cardiomyopathy is common in the same age group as insulinoma and should be ruled out
prior to anesthesia. Thoracic radiographs, ECG, occult heartworm testing and cardiac
ultrasound may be indicated.

Presurgical fasting is generally recommended for ferrets. Ferrets believed to have
insulinoma will be particularly prone to hypoglycemia and should be fasted for only 2 to 4
hours under observation. An IV drip of 2.5 to 5% dextrose with a balanced electrolyte
solution is indicated. Ferrets are excellent surgical candidates and tend to do well with many
anesthetic protocols. Isoflurane gas is currently the anesthetic of choice in the United
States.

A ventral midline incision is made beginning 3 to 4 cm caudal to the xyphoid process and
extending caudally to allow good visualization of the cranial and mid abdomen. The
pancreas is easily located adjacent to the duodenum. It is pale in color and has a right and
left limb. Insulinomas vary in size from 1 to 2 mm to, less commonly, 1 cm or more. There
may be one to several nodules in or on the pancreas. Insulinomas may be difficult to
visualize. The entire pancreas should be palpated gently for abnormalities in tissue density.
Insulinomas are usually firmer than the normal pancreatic tissue. These growths are often
darker red in color than the surrounding pancreatic tissue. Iris scissors are used to
carefully dissect around the abnormal tissue. The pancreas is handled gently to help
prevent post-surgical pancreatitis, although this sequela is uncommon in the ferret. The
tumor is removed and placed in formalin for histopathology.     Absorbable hemostatic
material may be used to prevent minor seepage from the surgical site. A 4-0 or 5-0
absorbable suture material may be used to ligate larger vessels in the pancreas. Partial
pancreatectomy would be recommended in cases where a large tumor is located at the end
of the pancreatic limb. Hemostatic clips are effectively used for this procedure. On

occasion, no individual nodules may be found, but the quantity of pancreatic tissue will be
several times that of a normal ferret.

The liver is biopsied for metastasis if irregularities are noted, and the adrenal glands,
mesenteric lymph nodes and spleen are examined for abnormalities before closing. Closure
is routine.

The blood glucose level should be checked immediately post-surgery and repeated several
times during the first 24 hours after the IV dextrose has been discontinued. The ferret
should be encouraged to eat as soon as it has recovered from anesthesia. Most ferrets will
remain euglycemic immediately post-surgically. Fasting blood glucose should be rechecked
7 to 10 days post-surgery and then every 2 to 4 months as long as the ferret remains
subclinical. Occasionally ferrets will remain hypoglycemic postsurgery. These ferrets
should be on prednisone therapy as needed. This has not been found to interfere with
healing.

LYMPHOMA

Lymphoma is common in two age groups, juveniles and older individuals, much as in cats.
The young ferret is often affected with mediastinal lymphoma and may present with
dyspnea, lethargy, and coughing. Peripheral lymphadenopathy is not usually noted in this
group.

Older ferrets with lymphoma have more variable presentations. Peripheral
lymphadenopathy does occur, but the practitioner should be cautious when palpating
peripheral lymph nodes to differentiate between the pronounced accumulation of fat that
commonly surrounds these lymph nodes (especially the prescapular and submandibular
nodes) and the actual nodes lying within the fat.22 Lymph node excision and submission for

histopathology is usually conclusive, whereas aspirates are difficult due to the surrounding
fat and the relatively small size of even enlarged nodes. The popliteal lymph node in ferrets
is easily accessible for resection and not as vascular as in dogs and cats. Splenic lymphoma
may occur, but without biopsy and histopathology it is difficult to diagnose due to the nearly
universal splenic enlargement (usually benign extra-medullary hematopoesis) that occurs as
ferrets of the U.S. gene pool as they age. Impression smears and FNA are often mistakenly
diagnosed as lymphoma due to the differing architecture in ferrets. Cardiac (hilar)
lymphadenopathy occurs with some frequency, and is often noted in conjunction with
cardiomyopathy on radiographs. Peripheral lymphocytosis may or may not occur, and the
finding of peripheral lymphoma cells on a blood smear is rare. Hepatic involvement is also
common, requiring biopsy for diagnosis. The finding of enlarged lymph nodes in the
intestinal mesentery, often encountered during a routine adrenalectomy, warrants a biopsy,
since lymphoma may be demonstrated in these nodes.1,2,13,14,18 However, mesenteric LN
enlargement is the rule rather than the exception in ferrets in the USA, and often is not
associated with current lymphoma, although these nodes may be suggestive of pre-
cancerous states. Protocols for chemotherapy have been used, and the option of treatment
with prednisolone alone exists, with generally the same positive and negative indications as
in the treatment for lymphoma in dogs and cats.13,16,18

Reverse transcriptase activity and retrovirus-like particles have been isolated from tissue of
affected ferrets in at least one “cluster” diagnosis of this neoplasia.25 Horizontal transmission
was then experimentally induced from affected ferrets via both cell culture and cell free
inoculation. Both clinical and pathologic findings indicate that a virally induced lymphoma is
present in some cases in ferrets, but further research is needed to confirm a viral etiology.

An acute presentation in young adult ferrets is also being noted with some frequency.
Specific clinical signs other than severe depression and fever are not yet documented.

Diagnosis in these cases is currently usually determined at necropsy.
Organomegaly/lymphadenopathy are not usually encountered.

OTHER NEOPLASIAS

Ferrets have a high incidence of neoplasia, including the previously discussed adrenal cell
tumors, insulinomas, and lymphoma. Cutaneous neoplasia is also common, including but
not limited to mast cell tumors, basal cell adenomas, adenocarcinomas and squamous cell
carcinomas.13,16,18 As a generalization, these cutaneous neoplasias may be recurrent, multi-
focal or isolated masses and they do not tend to metastasize to distant organs. Resection
as needed, with the general health of the patient, concurrent disease, and quality of life all
considered, is a prudent course of action.

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